neoadjuvant chemotherapy including sorafenib in women with previously untreated primary breast cancer

Conditions: Breast Cancer

Summary: the purpose of this study is to determine the efficacy and safety of sorafenib in the neoadjuvant setting in patients with primary breast cancer

epirubicin/cyclophosphamide followed by paclitaxel (ec/p) is a well tolerated regimen with high clinical activity. histopathological complete remission after preoperative chemotherapy has a direct correlation with the disease-free and overall survival. the aim of combining a chemotherapy regime with sorafenib in the neoadjuvant setting is to increase the locoregional and systemic outcome of these patients

Eligibility criteria:
inclusion criteria: * unilateral or bilateral primary carcinoma of the breast, * tumor lesion in the breast with a palpable size of \>= 2 cm. the lesion has to be measurable in two-dimensions preferably by sonography. in case of inflammatory disease the extent of inflammation can be used as measurable lesion; * patients should have stages of disease in which adjuvant chemotherapy would be considered. * women of childbearing potential must have a negative serum pregnancy test * negative her-2/neu status * karnofsky performance status index \>= 80%; * normal cardiac function * laboratory requirements: absolute neutrophile count (anc) \>= 2,0 x 109/l and platelets \>= 100 x 109/l and hemoglobin \>= 10 g/dl (\>= 6.2 mmol/l) inr ≤ 1.5 uln and ptt ≤ 1.5 uln within 14 days prior to enrolment asat or alat \ 1,5 x unl associated with alkaline phosphatase \> 2,5 x unl are not eligible for the study total bilirubin \< 1 x unl creatinine ≤ 175 µmol/l (2 mg/dl). the calculated creatinine clearance should be ≥ 60 ml/min. paraffin tumor tissue block and each one serum and one plasma sample centrally made available * complete staging work-up within 3 months prior to registration. * patients must be available and compliant for treatment and follow-up. patients registered on this trial must be treated and followed up at the participating or a cooperating center. exclusion criteria: * patients with low or moderate risk, which are only doubtful candidates for adjuvant chemotherapy and do not fulfil the inclusion criteria no. 5. * evidence of distant metastasis; * prior chemotherapy for any malignancy; * prior radiation therapy for breast cancer; * preexisting rhagades at hand and feet and other skin problems (e.g. psoriasis) * pregnant or lactating patients. * pre-existing motor or sensory neuropathy of a severity \>= grade 2 by nci criteria; 7. concurrent treatment with: chronic corticosteroids unless initiated \> 6 months prior to study entry and at low dose (\< 20 mg methylprednisolone or equivalent); sex hormones. prior treatment must be stopped before study entry; patients with increased risk of bleeding due to concurrent therapeutic or prophylactic anticoagulative treatment. low dose of coumarines are permitted. other experimental drugs or any other anti-cancer therapy; drugs recognized as being strong inhibitors or inducers of the isoenzyme cyp3a within the last 5 days or their expected need 8. other serious illness or medical condition: * previous malignant disease without being disease-free of less than 5 years (except cis of the cervix and non-melanomatous skin cancer) * known or suspected congestive heart failure (≥nyha ii) and/or coronary heart disease, angina pectoris requiring antianginal medication, previous history of myocardial infarction, evidence of transmural infarction on ecg, un- or poorly controlled arterial hypertension, rhythm abnormalities requiring permanent treatment, clinically significant valvular heart disease * thrombotic or embolic events * hemorrhage/bleeding event ≥ grade 3 within 4 weeks prior study entry * evidence or history of bleeding diathesis or coagulopathy * history of significant neurological or psychiatric disorders * patients with seizure disorders requiring medication such as steroids or antiepileptics * currently active infection * history of hiv infection or chronic hepatitis b or c * serious non healing wound, ulcer or bone fracture * patients with prior immunosuppressive treatment * severe pulmonary condition/illness * disease significantly affecting gastrointestinal function, * patients with severe liver disease * major surgery, open biopsy or significant traumatic injury within 4 weeks of first dose of study drug * definite contraindications for the use of corticosteroids * inadequate general condition (not fit for anthracycline/taxane-containing chemotherapy)

Keywords: neoadjuvant chemotherapy targeted therapy